NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise. (2nd June 2022)

• Record Type: Journal Article
• Authors: Hegazy, Shaymaa; Marques, Mariana C.; Canna, Scott W.; Goldbach-Mansky, Raphaela; de Jesus, Adriana A.; Reyes-Múgica, Miguel; Salgado, Claudia M.
• Is Part Of: American journal of dermatopathology. Volume 44:Number 6(2022)
• Page Start: e64
• Page End: e66
• Publication Date: 2022-06-02
• Subjects: fat necrosis of the newborn -- autoinflammatory diseases -- SAIDs -- NEMO; Skin -- Diseases -- Periodicals; Histology, Pathological -- Periodicals; 616.50705
• DOI: 10.1097/DAD.0000000000002144
• Languages: English
• ISSNs: 0193-1091

Abstract

Abstract: A 15-month-old full-term boy of African descent with an asymptomatic sickle cell trait presented with episodes of transient erythematous subcutaneous nodules involving the entire body except the face, since 2 weeks of age. The skin lesions evolved to areas of lipoatrophy and hyperpigmentation. An initial skin biopsy, studied at a different department at 2 months, was initially misinterpreted as subcutaneous fat necrosis of the newborn, despite the lack of the typical radiated crystals and needle-shaped clefts characterizing that entity. At 4 months of age, he developed systemic inflammatory manifestations, including fever, a new rash, significant periorbital edema, and failure to thrive. An extensive workup showed leukocytosis, hypercalcemia, elevated inflammatory markers, hypertriglyceridemia, and transaminitis. A new skin biopsy of the eyelid was diagnosed as neutrophilic lobular panniculitis with necrotic adipocytes. An initial whole-exome sequencing did not identify any causative mutations, but a WES reanalysis focused on autoinflammatory disorders was requested based on additional clinicopathologic data and revealed a mosaic intronic mutation in IKBKG c. 671+3 G > C. This mutation encodes an mRNA missing exon 5 resulting in NF-kB essential modulator (NEMO) Δ-exon 5–autoinflammatory syndrome (NDAS). NEMO-NDAS is one of the systemic autoinflammatory diseases that may appear as an unexplained panniculitis in young children, who should be monitored for immunodeficiency and/or autoinflammatory diseases. The differential diagnosis of autoinflammatory disorders should be considered in such cases incorporating the use of the whole-genome/exome sequencing in the investigation. The inhibitor of kappa-B kinase regulatory subunit gamma ( IKBKG ) is located on chromosome Xq28 and encodes the NEMO, a critical molecule upstream of NF-kB activation.